Sequential Methods in Multi-Arm Clinical Trials

Abstract

In this overview article, I will focus on adaptive designs in “learn” clinical studies, the exploratory phase of the drug development process designed and carried out in order to establish drug efficacy and dose-response relationships. These designs directly address the goals of the learn-phase trial with respect to identification of dose to carry forward in the confirmatory phase, estimation of likelihood of success in confirmatory trial, and efficient early stopping for efficacy or for futility. A critical component of these designs is the dose-response model for efficacy and/or safety endpoints that capture prior information about the form and location of the clinically important dose response relationship. An additional ingredient in the Bayesian approach is a prior distribution for unknown parameters. Efficiency is gained by appropriate incorporation of longitudinal models that allow the efficient use of all available information.